{"id":4472,"date":"2019-10-16T13:11:43","date_gmt":"2019-10-16T04:11:43","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=4472"},"modified":"2019-10-16T13:11:43","modified_gmt":"2019-10-16T04:11:43","slug":"cell-identity-reprogrammed","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4472","title":{"rendered":"Cell identity reprogrammed"},"content":{"rendered":"

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The discovery that cell differentiation can be reversed challenged theories of how cell identity is determined, laying the foundations for modern methods of reprogramming cell identity and promising new regenerative therapies.<\/h5>\n

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All cells of an organism derive from a single cell. As development progresses, cells become increasingly specialized to perform defined functions, a commitment that is accompanied by a restriction in the range of potential fates of those cells. In the late nineteenth century, a predominant thought was that, when they differentiate, cells retain only those pieces of heritable information required to maintain cell-type identity and function1<\/a><\/sup>. This led to the theory that differentiation is an irreversible process (Fig. 1a).\u00a0John Gurdon\u2019s seminal paper in\u00a0Nature<\/i><\/a>\u00a0on nuclear reprogramming of cell identity, with Tom Elsdale and Michael Fischberg2<\/a><\/sup>, provided a remarkable challenge to this dogma, and formed the basis for today\u2019s cell-reprogramming field.<\/p>\n

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Figure 1 | Key milestones in understanding the potential of differentiated cells.<\/b>\u2002a<\/b>, In 1892, Weismann proposed that, as cells in a developing embryo differentiate, they retain only those genes required to maintain cell-type identity, rendering differentiation an irreversible process1<\/a><\/sup>.\u00a0b<\/b>, Studying the Northern leopard frog (Rana pipiens<\/i>), Briggs and King reported5<\/a><\/sup>\u00a0in 1955 that nuclei from differentiated cells that were transferred into an egg cell from which the nucleus had been removed (an enucleated egg cell) could not support normal development, in line with Weismann\u2019s thinking.\u00a0c<\/b>, In their 1958\u00a0Nature<\/i>\u00a0paper2<\/a><\/sup>, Gurdon, Elsdale and Fischberg challenged the notion that development is irreversible, reporting that nuclei derived from differentiated cells of the African clawed frog (Xenopus laevis<\/i>) could, in fact, support normal development.\u00a0d<\/b>, In 2006, Takahashi and Yamanaka13<\/a><\/sup>\u00a0identified a core set of four transcription factors that reset differentiated mouse cells to a pluripotent state, capable of giving rise to any cell types in the body.<\/span><\/p>\n<\/figcaption><\/figure>\n

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Gurdon and colleagues\u2019 1958 paper was preceded by the work of Robert Briggs and Thomas King3<\/a><\/sup>. To investigate the developmental potential of differentiating cells, Briggs and King used a method called nuclear transfer, in which the nucleus is removed from one cell (in this case, an egg) and replaced with an intact nucleus from a different cell. Briggs and King\u2019s experiments were a technical feat that had previously been accomplished only in single-celled organisms4<\/a><\/sup>.<\/p>\n

Using this method in the more-complex Northern leopard frog (Rana pipiens<\/i>), they were able to produce normal, swimming tadpoles by replacing egg-cell nuclei with nuclei from blastomeres \u2014 cells that are made through the splitting of a fertilized egg cell during early development3<\/a><\/sup>. However, the transfer of nuclei from\u00a0R. pipiens<\/i>\u00a0cells at more-advanced stages of differentiation \u2014 from when the hollow ball of blastomeres differentiates into a multilayered structure called a gastrula, onwards \u2014 did not support the development of normal frogs5<\/a><\/sup>\u00a0(Fig. 1b).<\/p>\n

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